Glycemic Variability in Diabetes Increases the Severity of Influenza.
Identifieur interne : 000129 ( PubMed/Curation ); précédent : 000128; suivant : 000130Glycemic Variability in Diabetes Increases the Severity of Influenza.
Auteurs : Rebecca J. Marshall [Australie] ; Pornthida Armart [Australie] ; Katina D. Hulme [Australie] ; Keng Yih Chew [Australie] ; Alexandra C. Brown [Australie] ; Philip M. Hansbro [Australie] ; Conor J. Bloxham [Australie] ; Melanie Flint [Australie] ; Katharina Ronacher [Australie] ; Helle Bielefeldt-Ohmann [Australie] ; Linda A. Gallo [Australie] ; Kirsty R. Short [Australie]Source :
- mBio [ 2150-7511 ] ; 2020.
Abstract
People with diabetes are two times more likely to die from influenza than people with no underlying medical condition. The mechanisms underlying this susceptibility are poorly understood. In healthy individuals, small and short-lived postprandial peaks in blood glucose levels occur. In diabetes mellitus, these fluctuations become greater and more frequent. This glycemic variability is associated with oxidative stress and hyperinflammation. However, the contribution of glycemic variability to the pathogenesis of influenza A virus (IAV) has not been explored. Here, we used an in vitro model of the pulmonary epithelial-endothelial barrier and novel murine models to investigate the role of glycemic variability in influenza severity. In vitro, a history of glycemic variability significantly increased influenza-driven cell death and destruction of the epithelial-endothelial barrier. In vivo, influenza virus-infected mice with a history of glycemic variability lost significantly more body weight than mice with constant blood glucose levels. This increased disease severity was associated with markers of oxidative stress and hyperinflammation both in vitro and in vivo Together, these results provide the first indication that glycemic variability may help drive the increased risk of severe influenza in people with diabetes mellitus.IMPORTANCE Every winter, people with diabetes are at increased risk of severe influenza. At present, the mechanisms that cause this increased susceptibility are unclear. Here, we show that the fluctuations in blood glucose levels common in people with diabetes are associated with severe influenza. These data suggest that glycemic stability could become a greater clinical priority for patients with diabetes during outbreaks of influenza.
DOI: 10.1128/mBio.02841-19
PubMed: 32209691
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Marshall</name><affiliation wicri:level="1"><nlm:affiliation>School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD</wicri:regionArea></affiliation></author><author><name sortKey="Armart, Pornthida" sort="Armart, Pornthida" uniqKey="Armart P" first="Pornthida" last="Armart">Pornthida Armart</name><affiliation wicri:level="1"><nlm:affiliation>School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD</wicri:regionArea></affiliation></author><author><name sortKey="Hulme, Katina D" sort="Hulme, Katina D" uniqKey="Hulme K" first="Katina D" last="Hulme">Katina D. Hulme</name><affiliation wicri:level="1"><nlm:affiliation>School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD</wicri:regionArea></affiliation></author><author><name sortKey="Chew, Keng Yih" sort="Chew, Keng Yih" uniqKey="Chew K" first="Keng Yih" last="Chew">Keng Yih Chew</name><affiliation wicri:level="1"><nlm:affiliation>School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD</wicri:regionArea></affiliation></author><author><name sortKey="Brown, Alexandra C" sort="Brown, Alexandra C" uniqKey="Brown A" first="Alexandra C" last="Brown">Alexandra C. Brown</name><affiliation wicri:level="1"><nlm:affiliation>Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, New Lambton, NSW, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, New Lambton, NSW</wicri:regionArea></affiliation></author><author><name sortKey="Hansbro, Philip M" sort="Hansbro, Philip M" uniqKey="Hansbro P" first="Philip M" last="Hansbro">Philip M. Hansbro</name><affiliation wicri:level="1"><nlm:affiliation>Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, New Lambton, NSW, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, New Lambton, NSW</wicri:regionArea></affiliation></author><author><name sortKey="Bloxham, Conor J" sort="Bloxham, Conor J" uniqKey="Bloxham C" first="Conor J" last="Bloxham">Conor J. Bloxham</name><affiliation wicri:level="1"><nlm:affiliation>School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD</wicri:regionArea></affiliation></author><author><name sortKey="Flint, Melanie" sort="Flint, Melanie" uniqKey="Flint M" first="Melanie" last="Flint">Melanie Flint</name><affiliation wicri:level="1"><nlm:affiliation>School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD</wicri:regionArea></affiliation></author><author><name sortKey="Ronacher, Katharina" sort="Ronacher, Katharina" uniqKey="Ronacher K" first="Katharina" last="Ronacher">Katharina Ronacher</name><affiliation wicri:level="1"><nlm:affiliation>Mater Research Institute, Translational Research Institute, The University of Queensland, Woolloongabba, QLD, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Mater Research Institute, Translational Research Institute, The University of Queensland, Woolloongabba, QLD</wicri:regionArea></affiliation></author><author><name sortKey="Bielefeldt Ohmann, Helle" sort="Bielefeldt Ohmann, Helle" uniqKey="Bielefeldt Ohmann H" first="Helle" last="Bielefeldt-Ohmann">Helle Bielefeldt-Ohmann</name><affiliation wicri:level="1"><nlm:affiliation>School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD</wicri:regionArea></affiliation></author><author><name sortKey="Gallo, Linda A" sort="Gallo, Linda A" uniqKey="Gallo L" first="Linda A" last="Gallo">Linda A. Gallo</name><affiliation wicri:level="1"><nlm:affiliation>School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD</wicri:regionArea></affiliation></author><author><name sortKey="Short, Kirsty R" sort="Short, Kirsty R" uniqKey="Short K" first="Kirsty R" last="Short">Kirsty R. Short</name><affiliation wicri:level="1"><nlm:affiliation>School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia k.short@uq.edu.au.</nlm:affiliation><country wicri:rule="url">Australie</country><wicri:regionArea>School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD</wicri:regionArea></affiliation></author></analytic><series><title level="j">mBio</title><idno type="eISSN">2150-7511</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">People with diabetes are two times more likely to die from influenza than people with no underlying medical condition. The mechanisms underlying this susceptibility are poorly understood. In healthy individuals, small and short-lived postprandial peaks in blood glucose levels occur. In diabetes mellitus, these fluctuations become greater and more frequent. This glycemic variability is associated with oxidative stress and hyperinflammation. However, the contribution of glycemic variability to the pathogenesis of influenza A virus (IAV) has not been explored. Here, we used an <i>in vitro</i> model of the pulmonary epithelial-endothelial barrier and novel murine models to investigate the role of glycemic variability in influenza severity. <i>In vitro</i>, a history of glycemic variability significantly increased influenza-driven cell death and destruction of the epithelial-endothelial barrier. <i>In vivo</i>, influenza virus-infected mice with a history of glycemic variability lost significantly more body weight than mice with constant blood glucose levels. This increased disease severity was associated with markers of oxidative stress and hyperinflammation both <i>in vitro</i> and <i>in vivo</i> Together, these results provide the first indication that glycemic variability may help drive the increased risk of severe influenza in people with diabetes mellitus.<b>IMPORTANCE</b> Every winter, people with diabetes are at increased risk of severe influenza. At present, the mechanisms that cause this increased susceptibility are unclear. Here, we show that the fluctuations in blood glucose levels common in people with diabetes are associated with severe influenza. These data suggest that glycemic stability could become a greater clinical priority for patients with diabetes during outbreaks of influenza.</div></front></TEI><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">32209691</PMID><DateRevised><Year>2020</Year><Month>04</Month><Day>16</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2150-7511</ISSN><JournalIssue CitedMedium="Internet"><Volume>11</Volume><Issue>2</Issue><PubDate><Year>2020</Year><Month>Mar</Month><Day>24</Day></PubDate></JournalIssue><Title>mBio</Title><ISOAbbreviation>mBio</ISOAbbreviation></Journal><ArticleTitle>Glycemic Variability in Diabetes Increases the Severity of Influenza.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">e02841-19</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1128/mBio.02841-19</ELocationID><Abstract><AbstractText>People with diabetes are two times more likely to die from influenza than people with no underlying medical condition. The mechanisms underlying this susceptibility are poorly understood. In healthy individuals, small and short-lived postprandial peaks in blood glucose levels occur. In diabetes mellitus, these fluctuations become greater and more frequent. This glycemic variability is associated with oxidative stress and hyperinflammation. However, the contribution of glycemic variability to the pathogenesis of influenza A virus (IAV) has not been explored. Here, we used an <i>in vitro</i> model of the pulmonary epithelial-endothelial barrier and novel murine models to investigate the role of glycemic variability in influenza severity. <i>In vitro</i>, a history of glycemic variability significantly increased influenza-driven cell death and destruction of the epithelial-endothelial barrier. <i>In vivo</i>, influenza virus-infected mice with a history of glycemic variability lost significantly more body weight than mice with constant blood glucose levels. This increased disease severity was associated with markers of oxidative stress and hyperinflammation both <i>in vitro</i> and <i>in vivo</i> Together, these results provide the first indication that glycemic variability may help drive the increased risk of severe influenza in people with diabetes mellitus.<b>IMPORTANCE</b> Every winter, people with diabetes are at increased risk of severe influenza. At present, the mechanisms that cause this increased susceptibility are unclear. Here, we show that the fluctuations in blood glucose levels common in people with diabetes are associated with severe influenza. These data suggest that glycemic stability could become a greater clinical priority for patients with diabetes during outbreaks of influenza.</AbstractText><CopyrightInformation>Copyright © 2020 Marshall et al.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Marshall</LastName><ForeName>Rebecca J</ForeName><Initials>RJ</Initials><AffiliationInfo><Affiliation>School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Armart</LastName><ForeName>Pornthida</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hulme</LastName><ForeName>Katina D</ForeName><Initials>KD</Initials><AffiliationInfo><Affiliation>School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chew</LastName><ForeName>Keng Yih</ForeName><Initials>KY</Initials><AffiliationInfo><Affiliation>School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brown</LastName><ForeName>Alexandra C</ForeName><Initials>AC</Initials><AffiliationInfo><Affiliation>Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, New Lambton, NSW, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The University of Newcastle, Callaghan, NSW, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hansbro</LastName><ForeName>Philip M</ForeName><Initials>PM</Initials><AffiliationInfo><Affiliation>Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, New Lambton, NSW, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The University of Newcastle, Callaghan, NSW, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centre for Inflammation, Centenary Institute, Sydney, NSW, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>University of Technology Sydney, Faculty of Science, Ultimo, NSW, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bloxham</LastName><ForeName>Conor J</ForeName><Initials>CJ</Initials><Identifier Source="ORCID">https://orcid.org/0000-0003-1469-8174</Identifier><AffiliationInfo><Affiliation>School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Flint</LastName><ForeName>Melanie</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ronacher</LastName><ForeName>Katharina</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Mater Research Institute, Translational Research Institute, The University of Queensland, Woolloongabba, QLD, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bielefeldt-Ohmann</LastName><ForeName>Helle</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Australian Infectious Diseases Research Centre, The University of Queensland, St. Lucia, QLD, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gallo</LastName><ForeName>Linda A</ForeName><Initials>LA</Initials><AffiliationInfo><Affiliation>School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Mater Research Institute, Translational Research Institute, The University of Queensland, Woolloongabba, QLD, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Short</LastName><ForeName>Kirsty R</ForeName><Initials>KR</Initials><AffiliationInfo><Affiliation>School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia k.short@uq.edu.au.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Australian Infectious Diseases Research Centre, The University of Queensland, St. Lucia, QLD, Australia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>03</Month><Day>24</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>mBio</MedlineTA><NlmUniqueID>101519231</NlmUniqueID></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">blood glucose</Keyword><Keyword MajorTopicYN="N">diabetes</Keyword><Keyword MajorTopicYN="N">influenza</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>3</Month><Day>27</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>3</Month><Day>27</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>3</Month><Day>27</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32209691</ArticleId><ArticleId IdType="pii">mBio.02841-19</ArticleId><ArticleId IdType="doi">10.1128/mBio.02841-19</ArticleId><ArticleId 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